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[Methods of gene therapy for inner ear diseases].

OBJECTIVE: To study an effective, safety and convenient method for gene transfer and introduction to inner ear. METHOD: Ad GFP were transferred into inner ears of 30 guinea pigs through round window, basal turn of cochlea and cerebrospinal fluid respectively. Auditory brainstem response (ABR)and otoacoustic emission of distortion products (DPOAE) were assayed to these animals preoperatively and postoperatively, then transfection and expression of Ad-GFP in inner ears and structure of cochlear hair cells were observed. RESULT: Transfection and expression of Ad-GFP were found in spiral ganglion of cochlea, stria vascularis and Cortisorgan through all of the three methods. The expression products were in the highest level at the third day after operation. But the operation through round window and basal turn of cochlea could lead to bleeding and coagulum deposited in parietalgyrus, which could result in hair cells injury. Changes of ABR threshold of these animals were not significant. But amplitude of DPOAE decreased significantly in animals through round window and basal turn of cochlea pathways. There was no hair cells injury and changes of DPOAE through cerebrospinal fluid pathway. CONCLUSION: The study suggested the operations through round window and basal turn of cochlea could lead to bleeding in cochleas, which resulted in change of DPOAE amplitude. It is a safe and effective method to transfer through cerebrospinal fluid.

Animals↗

Use of transtympanic round window electrocochleography for threshold estimations in children.

OBJECTIVE: This study aimed to evaluate the efficacy of round window electrocochleography for the estimation of hearing thresholds in difficult-to-test children. STUDY DESIGN: The study was a retrospective analysis. SETTING: A standard day-stay operating room was used. PATIENTS: Round window electrocochleography was performed on 198 children between January 1993 and January 1996. INTERVENTION: The intervention was diagnostic. MAIN OUTCOME MEASURE: Clinically reliable pure-tone audiograms were obtained in 101 patients (50.9%) for comparisons of electrocochleography and behavioral thresholds. RESULTS: The mean differences between electrocochleography and behavioral thresholds at 0.5, 1, 2, and 4 kHz were less than 6 dB. Ninety-seven percent of the results were within +30 to -30 dB, and approximately 86% of the results were within +20 to -20 dB. Good correlation coefficients of 0.83, 0.84, 0.91 and 0.88 were found between electrocochleography and behavioral thresholds at 0.5, 1, 2, and 4 kHz, respectively. Only 2 of 395 ears were complicated postoperatively by suppurative otitis media. There were no anesthetic complications. CONCLUSION: Round window electrocochleography can be used in conjunction with other audiometric methods for threshold estimations in the difficult-to-test children and as part of the preoperative assessment for cochlear implantation.

Adolescent↗

The mechanism and site of action of lidocaine hydrochloride in guinea pig inner ear.

Lidocaine was applied to the round window (RW) in order to localize its site of action in the cochlea. Cochlear microphonic (CM), summating potential (SP), and compound action potential (CAP) input/output functions were measured to a 16 kHz tone burst to assess the functional changes of the cochlea. In separate experiments, the effect of lidocaine on the whole cell current of isolated outer hair cells (OHC) was studied. A dose of 2 microliters of 40 mM lidocaine in saline solution, when applied to the RW, caused a small change in all measured variables, indicating a passage of the drug through the RW membrane to sites of action. However, 160 mM of lidocaine further decreased CM, SP, and CAP by a total of 40% from the control. A partial recovery occurred for CM during the 30 min follow-up period. CAP and SP continued to decline. In isolated OHCs, lidocaine decreased the whole cell current in a dose-dependent fashion. The KD for lidocaine effect on OHCs was 7 mM. Our in vivo results indicate that lidocaine affects OHCs and reduces CM, causing a subsequent reduction in SP and CAP. The increased effect of lidocaine on CAP and SP, while CM is recovering, suggests an additional specific effect of lidocaine on the cochlear nerve and/or on inner hair cells. Considering that lidocaine alters OHC current (in isolated hair cells) and that lidocaine does not affect endocochlear potential [Laurikainen et al. Acta Otolaryngol (Stockh) 1991: 112: 800-9], the observed CM changes are most likely due to an in vivo effect on OHCs. Thus, the early effect of lidocaine on the cochlea appears to be due to a significant change in organ of Corti function, rather than to direct anesthesia of the cochlear nerve. Later, an independent effect of the drug may occur on neural tissues in the inner ear.

Animals↗

The effect of superior canal dehiscence on cochlear potential in response to air-conducted stimuli in chinchilla.

A superior semicircular canal dehiscence (SCD) is a break or hole in the bony wall of the superior semicircular canal. Patients with SCD syndrome present with a variety of symptoms: some with vestibular symptoms, others with auditory symptoms (including low-frequency conductive hearing loss) and yet others with both. We are interested in whether or not mechanically altering the superior canal by introducing a dehiscence is sufficient to cause the low-frequency conductive hearing loss associated with SCD syndrome. We evaluated the effect of a surgically introduced dehiscence on auditory responses to air-conducted (AC) stimuli in 11 chinchilla ears. Cochlear potential (CP) was recorded at the round-window before and after a dehiscence was introduced. In each ear, a decrease in CP in response to low frequency (<2 kHz) sound stimuli was observed after the introduction of the dehiscence. The dehiscence was then patched with cyanoacrylate glue leading to a reversal of the dehiscence-induced changes in CP. The reversible decrease in auditory sensitivity observed in chinchilla is consistent with the elevated AC thresholds observed in patients with SCD. According to the 'third-window' hypothesis the SCD shunts sound-induced stapes velocity away from the cochlea, resulting in decreased auditory sensitivity to AC sounds. The data collected in this study are consistent with predictions of this hypothesis.

Acoustic Stimulation↗

Review of round window membrane permeability.

The round window membrane (RWM) is permeable to certain biological substances. Those substances that can pass through the RWM have the potential to cause inner ear damage, leading to functional disturbances. The RWM is permeable to water, and the existence of osmotically active substances in the middle ear cavity can induce an alteration of inner ear fluid osmolality, leading to membrane displacement. However, several limiting factors exist that prevent free passage of substances from the middle ear to the inner ear. These include the morphological barrier of the three-layered RWM, the molecular weight of the substances, and the nature and concentration of substances in the middle ear cavity. The degree and duration of the inflammation in the middle ear cavity, as well as the morphological integrity of the RWM, also play an important role in controlling the passage of noxious substances into the inner ear. Further characterization of the factors involved in RWM permeability, and clarification of the mechanisms of the inner ear damages caused by substances passing into the inner ear through the RWM, are necessary for an understanding of the inner ear dysfunction caused by middle ear inflammation.

Animals↗

Histopathologic study of the perilymph-suctioned labyrinth.

A small amount of perilymph was suctioned from the scala tympani through the round window membrane of guinea pigs. The animals either were killed immediately after the suctioning or were kept alive for 1 to 3 months. For morphologic study, the conventional celloidin embedding method was employed, and the temporal bones were serially sectioned. Various kinds and degrees of changes in the membranous labyrinth were observed: hydrops, collapse, and rupture. Loss of outer hair cells in the upper turns of the cochlea was noted in the 1- to 3-month recovery specimens. These findings are identical to those found in animals in which artificial perilymph was injected into the subarachnoid space in order to produce experimental perilymphatic fistula. After comparing morphologic changes of the membranous labyrinth following use of each method, we concluded that perilymph suctioning from the round window can be used as an animal model of perilymphatic fistula.

Animals↗

Cochlear aqueduct flow resistance depends on round window membrane position in guinea pigs.

The resistance for fluid flow of the cochlear aqueduct was measured in guinea pigs for different positions of the round window membrane. These different positions were obtained by applying different constant pressures to the middle ear cavity. Fluid flow through the aqueduct was induced by small pressure steps superimposed on these constant pressures. It was found that the resistance for fluid flow through the aqueduct depended on the round window position but not on flow direction. The results can be explained by special fibrous structures that connect the round window with the entrance of the aqueduct. It was also found that the equilibrium inner ear pressure depends on middle ear pressure, indicating that the aqueduct does not connect the inner ear with a cavity with constant pressure.

Animals↗

Early alterations of cochlear function in experimental perilymph fistulas.

Alterations of cochlear function secondary to perforation of the round window membrane in guinea pigs were expected to reveal sensitive and/or specific audiometric parameters in perilymph fistulas. A perforation of the round window membrane either did not affect acoustic compound action potential thresholds, or induced a delayed, possibly conductive, inner ear hearing loss. Also, evoked suprathreshold responses deteriorated progressively and independently of the increase of compound action potential thresholds. A sudden (conductive) hearing loss and a poor response to suprathreshold stimulation might indicate inner ear damage secondary to a perilymphatic fistula.

Animals↗

Permeability of the round window membrane to middle-sized molecules in purulent otitis media.

The effect of pneumococcal otitis media on the permeability of the round window membrane was evaluated using tetraethylammonium ions as a tracer. Round window membrane permeability is reduced significantly at resolved stages of purulent otitis media. In contrast, measurements of round window membrane permeability indicate that acute purulent otitis media has a tendency to facilitate such permeability. Moreover, histologic observations of the round window membrane following bacterial inoculation further support the evidence of functional changes in round window membrane permeability. These findings indicate that the round window membrane in resolved stages of purulent otitis media plays a protective role in preventing the penetration of harmful substances into the inner ear.

Animals↗

Role of transtympanic endoscopy of the middle ear in the diagnosis of perilymphatic fistula in patients with sensorineural hearing loss or vertigo.

BACKGROUND: The diagnosis of perilymphatic fistula (PLF) is often difficult, and therefore the condition can be overlooked. Tympanoscopy presents an alternative procedure for visualising the middle ear anatomy, and it may help to diagnose PLF. AIM: The aim of this study was to evaluate the use of middle ear endoscopy in establishing the diagnosis of PLF and in defining its incidence in patients with sensorineural hearing loss and/or vertigo and tinnitus. SUBJECTS AND METHODS: Two hundred and sixty-five patients (22-80 years of age, mean 48 years) were prospectively and consecutively referred for middle ear examination with tympanoscopy. Tympanoscopy was performed using endoscopes with visual angles of 5 and 25 degrees and an outer diameter of 1.7 mm. The round window niche (with its secondary membrane), the oval window with a stapes superstructure, a part of the facial recess and the area in the fissula ante fenestram were examined and video-recorded. RESULTS: For 1 patient, tympanoscopy revealed fistula in the round window membrane that was covered with a fibrinous layer. In 4 cases abnormal mucosal shining appeared in the round window, but no PLF was present. In 7 cases the tympanic cavity could not be visualised because of the adhesive tympanic membrane, abnormal anatomy or the prominent exostoses of the external ear canal. In 6 cases a postendoscopic middle ear infection was found. No permanent tympanic membrane perforation occurred in any of the patients in this study. CONCLUSIONS: Tympanoscopy is a rapid examination tool with which to verify certain areas of the middle ear anatomy, but it is of limited value for ruling out the presence of PLF.

Adult↗

Mechanism of hearing disturbance due to alteration in atmospheric pressure.

We used a soundproof pressure chamber to examine how the changes in atmospheric pressure as experienced in daily life reduces bone conduction in a total of 48 normal adults. The subjects were given special ear plugs that connected external auditory canal to the pressure gauge and a small pump located outside the chamber, and were instructed not to swallow, to avoid active opening of the Eustachian tube. The chamber pressure was increased (or decreased) to +/- 500 mmH2O at a rate of 33 mmH2O/s. Then pressure in the external auditory canal was increased (or decreased) gradually after the chamber pressure had reached +/- 500 mmH2O, to equilibrate the pressure across the ear drum. Bone conduction did not recover the level before increase (or decrease) in the chamber pressure. We conclude that at least a minor part of the deterioration in bone conduction after changes in the chamber pressure was caused by displacement of the round window membrane.

Adult↗

[Microperforation and removal of the round window membrane. Short- and long-term study in animal experiments using electrocochleography and evoked response audiometry].

Our earlier animal experiments on guinea pigs showed that instrumental perforation of the round window membrane by a 0.2 mm platinum wire leads to an instant loss of the inner ear functions. The membrane defect healed in a few days, the cochlear structures remained intact, and the compound action potential of the auditory nerve and the brain-stem responses could be evoked again with normal latency times within 2 weeks. 1. In the studies reported here we first carried out microperforations with a 1 micron needle electrode, which caused no changes of the hearing potentials (cochlear microphonics, compound action potential of the auditory nerve, brain-stem responses), and no visible defect of the round window membrane and no perilymph outflow. 2. The removal of the round window membrane and the withdrawal of the perilymph led to a loss of the cochlear microphonics and to a considerable increase of the latency times of wave I (Jewett). The hearing potential regained their original values after 2 weeks without closure of the round window niche. The round window membrane had regenerated spontaneously and the scala tympani was again filled with perilymph. After covering the round window niche with a connective tissue graft, the hearing potentials regained their original values after 2 weeks, as they had done without cover of the round window niche. The round window membrane regenerated below the tissue graft and the scala tympani was also filled again with perilymph.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Computed tomography data based rapid prototyping model of the temporal bone before cochlear implant surgery.

Rapid prototyping (RP) technique allows automatic fabrication of 3D model parts. This method was applied to make a temporal bone model before cochlear implant surgery. A helical CT scan is used to acquire high resolution data from the middle and the inner ear of the patient. From the scanning data bone structures and soft tissues can be separated because their different grayscale pixel values. By using a guided image processing tool the desired parts of the anatomy can be extracted and 3D data created. The segmented data are processed to the form suitable for creating a high accuracy RP model. The RP model is made in the stereolithography (SLA) process by means of a computer guided HeCd laser beam inducing polymerisation of acrylic solution as it passes layer by layer over the surface of the polymer solution. In this prototype model the anatomy of the temporal bone can be clearly visualised, including, e.g., mastoid cells, tympanic cavity, bony canal of facial nerve, and round and oval windows. The inner ear spaces including vestibule, semicircular canals and cochlear turn are also shaped. The transparent acrylic material allows bonelike mechanical handling. The RP model can be dissected and used in individual surgical planning and simulation prior to cochlear implantation.

Cochlear Implants↗

[Lesions of round window membrane].

In 15 cases, a rupture of the round window membrane could be found via exploratory tympanotomy. The main sign in these cases was an inner ear deafness; vertigo and tinnitus were less frequent. These findings correspond well with reports in the literature. Since there is no specific clinical sign of a ruptured membrane, tympanotomy is necessary in all suspicious cases. Chances of restoration or maintenance of hearing are high in cases of early repair of the fistula, but prospects diminish as the time interval between injury and repair increases. Vertigo and tinnitus disappear even by a delayed operation. The healing process of the round window membrane and the pathological changes in the round window niche after ruptured membrane were studied in guinea pigs. To evaluate the relationship between round window membrane rupture and blunt head injury, 87 temporal bones were studied after a fatal head injury.

Animals↗

[Permeability of the round window membrane for prednisolone-21-hydrogen succinate. Prednisolone content of the perilymph after local administration vs. systemic injection].

BACKGROUND AND OBJECTIVE: Prednisolone is the drug of first choice for the treatment of cochleovestibular disorders, such as sudden hearing loss. Because of the known side effects, the efficient drug levels to be achieved within inner ear fluids are limited by intravenous administration. The aim of the study was to determine the concentration in the perilymph of prednisolone-21-hydrogen succinate applied into the round window niche in comparison to the concentration after intraperitoneal application. METHODS: Application of prednisolone-21-hydrogen succinate (5 mg in 0.1 ml) on the round window membrane was performed after sedation under microscopic view directly into the round window niche of the guinea pig. In order to compare the results, perilymph samples after systemic application of 60 mg/kg body weight prednisolone were used. The time between application and taking specimens of perilymph from the cochlea varied. Specimens of perilymph were obtained after 15, 20, 80, 180, 330, and 960 min (10 specimens in each group, n = 60) by dissecting the cochlea and opening the apex cochleae. Levels of prednisolone-21-hydrogen succinate in perilymph were measured by isocratic high-pressure liquid chromatography (HPLC). RESULTS: The highest levels of prednisolone-21-hydrogen succinate were found after 180 min: 952.3 mg/l (95% confidence interval: 382.7). After 960 min the level was 18.72 mg/l (95% confidence interval: 16.9). In the group with systemic application, the levels measured were below 14.71 mg/l (95% confidence interval: 7.05). CONCLUSION: The results demonstrate that high levels of prednisolone-21-hydrogen succinate in perilymph are achievable by local application of a single dose into the round window niche. After application of 5 mg, the levels of prednisolone are measurable up to 16 h.

Administration, Topical↗

[The clinical observations on 110 cases of adhesive otitis media].

The treatment of the adhesive otitis media (AOM) remains a challenge to the otologists. This paper analysed 110 cases of AOM (120 ears) collected during 25 years from 1967 to 1992. The clinical observation found that the lesions of AOM affected all parts of the middle ear, even the round and oval windows. There were various degrees of tympanic fibrous adhesions and atelectatic tympanum in these cases. After the tympanic adhesions were surgically separated and the lesions were removed, the silastic film or a slice of the homologous cartilages were put into the tympanum to prevent a new adhesion. It was showed that the silastic film was frequently enveloped in a capsule formed by the fibrous collagenous tissue and other extensive adhesions were existed around the capsule. But the cartilage slice caused the slighter pathological reactions. However, their hearing did not recovery to an available level. Therefore the further studies for the treatment of AOM are necessary.

Adolescent↗

Neuroprotective Drug Therapy: A Medical and Pharmacological Treatment for Tinnitus Control.

The role of neuroprotective agents for maintaining or improving inner ear function, specifically for the symptom of tinnitus, is presented on the basis of neurootological, neurological, and neurosurgical clinical experiences. These clinical experiences involved the use of calcium channel blockers, free radical scavengers, corticosteroids, antagonists of glutamate at N-methyl-D-aspartate (NMDA) and non-NMDA receptors, and various thrombolytic agents for the etiologies of ischemia, trauma, and hemorrhage. A pharmacological basis for such drug efficacy includes a property described as neuroprotection. A pathology-based protocol for drug selection is proposed for tinnitus control. The goal of this article is to introduce to the neurootologist or otologist and other professionals attempting tinnitus control neuroprotective drug therapies that are being applied to such central nervous system pathological processes as ischemia, trauma, hemorrhage, and neurodegeneration. The innovative application of such drug therapies for treating the symptom of tinnitus of the severe disabling type is considered. The use of neuroprotective drugs in intratympanic drug therapy via the round window, for treatment of inner ear complaints of hearing loss, tinnitus, and vertigo, is discussed.

Journal Article↗

Round window membrane permeability during experimental purulent otitis media: altered Cortisporin ototoxicity.

Round window membrane (RWM) permeability is the most critical factor influencing cochlear function following otitis media. Because otic drops are frequently used during purulent otitis media (POM), we investigated RWM permeability and ototoxicity of Cortisporin otic suspension after inducing experimental POM. Unilateral POM was induced in eight chinchillas by inoculating type 7F Streptococcus pneumoniae into the right ears. Left ears were inoculated with phosphate-buffered saline (control). When POM resolved, the animals were divided into two groups. The round window niches of group 1 were covered with Cortisporin otic suspension. Compound action potentials were measured before and after drug application. The RWM permeability was measured in group 2 by use of tetraethylammonium (TEA) ions as tracers, and the arrival time of TEA and the slope of the potassium-selective microelectrode response were measured. Animals with otitis media exhibited less susceptibility to ototoxicity of Cortisporin otic suspension and reduced RWM permeability to the medium-sized molecule TEA.

Animals↗